Despite great advances in research and treatment, the occurrence and mortality of ovarian cancer remains high. Each year, about 22,000 women in the United States are diagnosed with ovarian cancer. Currently, the standard treatment for Stage IV ovarian cancer consists of both surgery and chemotherapy. Unfortunately, less than 10% of patients experience long-term survival following standard treatment (Barnett et al., Cancer 119:3653-3661, 2013; Phippen et al., Gynecol Oncol 131:158-162, 2013; Zhidkov et al., Mol Pharm. 10(9): 3315-22, 2013) because advanced stage ovarian cancer is difficult to completely remove with surgery and currently available chemotherapy is unable to eradicate all of the remaining cancer cells (Colombo, Future Oncol 9:19-23; colombo et al., Crit Rev Oncol Hematol. 89(2):207-16, 2014; Rooth, Br J Nurs. 22(17):523-30, 2013).
Follicle-stimulation hormone (FSH, follitropin) is released by the pituitary gland and is associated with reproduction and the development of eggs in women and sperm in men. This hormone belongs to a family of heterodimeric glycoproteins together with luteinizing hormone (LH; lutropin), chorionic gonadotropin (CG; choriogonadotropin), and thyroid-stimulating hormone (TSH; thyrotropin). The FSH heterodimer protein comprises an alpha and a beta subunit. The alpha subunit is encoded by a single gene and can be interchanged between hormones without effect on receptor binding, whereas the beta subunits differ and direct binding specificity. Follicle-stimulation hormone receptor (FSHR) is a seven-transmembrane G-protein-coupled receptor, which interacts with follicle-stimulation hormone (FSH).
In healthy adult humans, FSHR is expressed only in the granulosa cells of the ovary, Sertoli cells of the testis, and a minimal expression is observed in the endothelial cells of gonadal blood vessels. Recently several reports have documented the expression of FSHR in 50-70% of ovarian cancer tissues, as well as other types of tumors including; renal cell carcinoma, prostate, breast, colon, pancreas, urinary bladder, kidney, lung, liver, stomach, testis. Notably, FSHR protein is also selectively expressed on the surface of the blood vessels of a wide range of tumors e.g., renal cell carcinoma, prostate, breast, colon, pancreas, urinary bladder, kidney, lung, liver, stomach, testis, and ovary (primary tumor and/or metastases) (Radu et al., N Engl J Med 363:1621, 2010; Siraj et al., BMC Cancer 13:246, 2013; and Renner et al., Histopathology 63:29, 2013). FSH receptors are important in tumor angiogenesis by signaling via two pathways, one involving VEGF, and a Gq/11 mechanism that activates VEGFR-2 independently of VEGF. The relative specific expressions of FSHR on cell surface of malignant tissues make it an attractive target for FSHR tumor immunotherapy.
Immunotherapy is a promising approach for cancer treatment thanks to the potential of the immune system to target tumors without the toxicity associated with traditional chemo-radiation. However, there is an urgent need for a more targeted antigen-specific immunotherapy for treatment of certain cancers, such as, for example, ovarian cancer. The present invention addresses this need.